University of British Columbia, Vancouver, British Columbia, Canada.
Ann Hepatol. 2012 Mar-Apr;11(2):179-85.
Chronic hepatitis C virus (HCV) is a major problem affecting up to 170 million people worldwide. Two protease inhibitors have recently been approved that will revolutionize treatment. Our objective was to summarize and evaluate the literature pertaining to the pharmacokinetics of boceprevir and telaprevir, in order to provide clinicians with insight into the management of actual and potential drug interactions.
A standardized search using MEDLINE (1948-November 2011), EMBASE (1980-November 2011), IPA (1970-November 2011), Google, and Google Scholar that combined the search terms boceprevir, telaprevir, pharmacokinetics, drug interaction, and drug metabolism was performed. Manual reference searches of chosen articles were completed. Monographs and articles, conference proceedings, and abstracts were evaluated. Boceprevir and telaprevir are both substrates and inhibitors of cytochrome P450 3A4 and telaprevir is a substrate of p-glycoprotein. Levels of boceprevir are decreased in patients taking efavirenz but effects with other antiretrovirals are minimal or unknown. Coadministration with efavirenz may compromise telaprevir levels and should be avoided. Telaprevir may increase levels of cyclosporine, tacrolimus, atorvastatin, and amlodipine, which may expose patients to increased adverse effects. Conclusions. Significant drug-drug interactions occur with both boceprevir and telaprevir. Until studies are reported and experience is gained with these agents, clinicians will need to be careful when administering in high-risk populations and those receiving chronic therapy with interacting agents. Studies are urgently needed in HIV patients taking antiretrovirals and patients taking chronic immunosuppression as these populations are at increased risk of experiencing clinically significant interactions.
慢性丙型肝炎病毒（HCV）是全球影响多达 1.7 亿人的主要问题。最近批准了两种蛋白酶抑制剂，这将彻底改变治疗方法。我们的目的是总结和评估博赛泼维与特拉泼维的药代动力学文献，以便为临床医生提供有关管理实际和潜在药物相互作用的深入了解。
使用 MEDLINE（1948 年-2011 年 11 月）、EMBASE（1980 年-2011 年 11 月）、IPA（1970 年-2011 年 11 月）、Google 和 Google Scholar 进行了标准化搜索，其中结合了博赛泼维、特拉泼维、药代动力学、药物相互作用和药物代谢等搜索词。完成了对选定文章的手动参考文献搜索。评估了专论和文章、会议记录和摘要。博赛泼维和特拉泼维均为细胞色素 P450 3A4 的底物和抑制剂，而特拉泼维是 p-糖蛋白的底物。接受依非韦伦治疗的患者博赛泼维水平降低，但与其他抗逆转录病毒药物的作用最小或未知。与依非韦伦合用可能会降低特拉泼维水平，应避免合用。特拉泼维可能会增加环孢素、他克莫司、阿托伐他汀和氨氯地平的水平，这可能会使患者面临增加的不良反应风险。结论：博赛泼维和特拉泼维均会发生显著的药物相互作用。在这些药物的研究报告和经验积累之前，临床医生在为高风险人群和接受相互作用药物的慢性治疗的患者给药时需要谨慎。在接受抗逆转录病毒药物治疗的 HIV 患者和接受慢性免疫抑制治疗的患者中，迫切需要进行研究，因为这些人群发生具有临床意义的相互作用的风险增加。
